Multiple Sclerosis (MS), a chronic inflammatory neurodegenerative disease, is accompanied by a number of comorbidities. Among the psychiatric ones, depression and anxiety occupy a special place. It is estimated that the prevalence of anxiety in the MS population is 22.1% verus 13% in the general population; whereas the prevalence of anxiety levels, as determined by various questionnaires, reaches even 34.2%. Systematic literature reviews (SPL) show considerable data variations due to differences in study design, sample size, diagnostic criteria and extremely high heterogeneity (I2). Among the more conspicuous factors associated with anxiety disorder in MS are demographic factors (age and gender), nonsomatic depressive symptoms, higher levels of disability, immunotherapy treatments, MS type, and unemployment. Depression is the most common psychiatric commorbidity in MS and the lifetime risk of developing depression in MS patients is >50%. According to some research, the prevalence of depression in MS vary between 4.98% and 58.9%, with an average of 23.7% (I2=97.3%). Brain versus spinal cord lesions, as well as temporal lobe, fasciculus arcuatus, superior frontal and superior parietal lobe lesions in addition to the cerebral atrophy have been shown to be the anatomical predictors of depressive disorder in MS. Hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) and the consequent dexamethasone-insupressible hypercortisolemia, in addition to cytokine storm (IL-6, TNF-α, TGFβ1, IFNγ/IL-4) present the endocrine and inflammatory basis for development of depression. Fatigue, insomnia, cognitive dysfunction, spasticity, neurogenic bladder, pain, and sexual dysfunction have shown to be additional precipitating factors in development of anxiety and depression in MS patients.